Natural antibodies to IFN-gamma in man and their increase during viral infection.
Natural antibodies to IFN-gamma were found in healthy individuals ranging from newborn babies to adults and, at higher levels, in patients suffering from different viral infections. During a viral infection, the titer of anti-IFN-gamma antibodies was observed to be correlated with the stage of the disease. Antibodies specific to IFN-gamma were affinity purified both from sera taken from healthy individuals and sera from viral-infected patients, by using a rIFN-gamma-coupled CNBr-activated Sepharose 4B column. The antibodies were found to be of the IgG class, and maintained their ability to bind rIFN-gamma. They were then tested for neutralizing activity and none of the IgG preparations we analyzed impaired the antiviral activity of rIFN-gamma. This finding suggests that the antigenic determinants recognized by these antibodies on the IFN-gamma molecule are located outside the site, on the IFN-gamma molecule, responsible for its antiviral activity.


[Outpatient rehabilitation of postinfarct heart failure].
Patients who had had myocardial infarction complicated by the initial stages of cardiac insufficiency were tested for capacity for work and haemodynamics while undergoing outpatient rehabilitation. A rehabilitation program is offered based on self-training under periodic control, which consists in individual walks and medical gymnastics. Patients undergoing rehabilitation compared to the control groups show statistically significant decrease of symptoms of cardiac insufficiency, enhanced physical capacity for work, improved haemodynamics. This rehabilitation program can be recommended for patients with initial stages of cardiac insufficiency.


A Department of Social Work uses data to prove its case [corrected].
The introductions of managed care with its emphasis on cost containment has led a Department of Social Work Services at a large urban teaching center to better document and justify its roles. A concrete result was the saving of social work positions during budget cutbacks and downsizing. There is also information in these data to help clarify the differential roles of social workers and utilization review nurses in the hospital case management/discharge planning processes. The system came about because of concerns around cost containment, the need for more systematic discharge planning and the advent of the Prospective Payment System and Diagnosis Related Groups (DRG's) as a means of reimbursement to hospitals.


A teaching file, using 10 X 10 cm format copies.
A teaching file is of paramount importance for a teaching department. It should be easily accessible and readily available. Considerations of costs and available space influence the choice of film size for the copies. We have chosen for 10 X 10 cm copies, because the majority can be viewed by individuals on normal lightboxes, while for larger audiences various ways of projection are feasible. The possibility, offered by the Delcomat copying apparatus, of making copies of interesting parts of the original film in varying degrees of reduction in size, enhances the practicability of the method.


The transfer of mannose from guanosine diphosphate mannose to dolichol phosphate and protein by pig liver endoplasmic reticulum.
When pig liver microsomal preparations were incubated with GDP-[(14)C]mannose, 10-40% of the (14)C was transferred to mannolipid and 1-3% to mannoprotein. The transfer to mannolipid was readily reversible and GDP was one of the products of the reaction. It was possible to reverse the reaction by adding excess of GDP and to show the incorporation of [(14)C]GDP into GDP-mannose. When excess of unlabelled GDP-mannose was added to a partially completed incubation there was a rapid transfer back of [(14)C]mannose from the mannolipid to GDP-mannose. The other product of the reaction, the mannolipid, had the properties of a prenol phosphate mannose. This was illustrated by its lability to dilute acid but stability to dilute alkali, and by its chromatographic properties. Dolichol phosphate stimulated the incorporation of [(14)C]mannose into both mannolipid and into protein, although the former effect was larger and more consistent than the latter. The incorporation of exogenous [(3)H]dolichol phosphate into the mannolipid, and its release, accompanied by mannose, on treatment of the mannolipid with dilute acid, confirmed that exogenous dolichol phosphate can act as an acceptor of mannose in this system. It was shown that other exogenous polyprenol phosphates (but not farnesol phosphate or cetyl phosphate) can substitute for dolichol phosphate in this respect but that they are much less efficient than dolichol phosphate in stimulating the transfer of mannose to protein. Since pig liver contained substances with the chromatographic properties of both dolichol phosphate and dolichol phosphate mannose, which caused an increase in transfer of [(14)C]mannose from GDP-[(14)C]mannose to mannolipid, it was concluded that endogenous dolichol phosphate acts as an acceptor of mannose in the microsomal preparation. The results indicate that the mannolipid is an intermediate in the transfer of mannose from GDP-mannose to protein. Some 4% of the mannose of a sample of mannolipid added to an incubation was transferred to protein. A scheme is proposed to explain the variations with time in the production of radioactive mannolipid, mannoprotein, mannose 1-phosphate and mannose from GDP-[(14)C]mannose that takes account of the above observations. ATP, ADP, UTP, GDP, ADP-glucose and UDP-glucose markedly inhibited the transfer of mannose to the mannolipid.


Distinct Roles of Dopamine Receptor Subtypes in the Nucleus Accumbens during Itch Signal Processing.
Ventral tegmental area (VTA) dopaminergic neurons, which are well known for their central roles in reward and motivation-related behaviors, have been shown to participate in itch processing via their projection to the nucleus accumbens (NAc). However, the functional roles of different dopamine receptor subtypes in subregions of the NAc during itch processing remain unknown. With pharmacological approaches, we found that the blockade of dopamine D1 receptors (D1R), but not dopamine D2 receptors (D2R), in the lateral shell (LaSh) of the NAc impaired pruritogen-induced scratching behavior in male mice. In contrast, pharmacological activation of D2R in both the LaSh and medial shell (MeSh) of the NAc attenuated the scratching behavior induced by pruritogens. Consistently, we found that dopamine release, as detected by a dopamine sensor, was elevated in the LaSh rather than the MeSh of the NAc at the onset of scratching behavior. Furthermore, the elevation of dopamine release in the LaSh of the NAc persisted even though itch-relieving behavior was blocked, suggesting that the dopamine signal in the NAc LaSh represents a motivational component of itch processing. Our study revealed different dynamics of dopamine release that target neurons expressing two dopamine receptors subtypes within different subregions of the NAc, and emphasized that D1R in the LaSh of the NAc is important in itch signal processing.SIGNIFICANCE STATEMENT Dopamine has been implicated in itch signal processing. However, the mechanism underlying the functional role of dopamine in itch processing remains largely unknown. Here, we examined the role of dopamine D1 receptor (D1R) and D2R in the nucleus accumbens (NAc) shell during pruritogen-induced scratching behavior. We demonstrated that D1R in the NAc lateral shell (LaSh) play an important role in motivating itch-induced scratching behavior, while activation of D2R would terminate scratching behavior. Our study revealed the diverse functional roles of dopamine signals in the NAc shell during itch processing.


The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder.
To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS). Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes. The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children.


THE INCIDENCE OF SPORTS INJURIES AMONG SCHOOL-AGED CHILDREN AND ADOLESCENTS.
It is estimated that approximately one in ten school-aged children experience sports-related injuries annually. These injuries are most common at 12 years of age. Boys are more likely to get injured and more likely to get seriously injured than girls. The probability of injury is greater in contact or high-impact sports, with American soccer accounting for the largest number of injuries, followed by wrestling, basketball, soccer, and baseball. In certain sports, such as horseback riding, women are four times more likely to sustain injuries. The presented literature review details the incidence of various sports-related injuries in adolescents. Sports-related injuries observed in children under the age of 10 are nonspecific and include contusions, mild sprains, and fractures of the extremities, most commonly Salter-Harris fractures (growth plate fractures) or plastic fractures. In young athletes, sports-related injuries of the ligaments or muscles, as well as spinal or head injuries, are rare. This is particularly true during puberty, where growth plate fractures and musculoskeletal injuries occur more frequently.


Relationship of solo status, academic rank, and perceived distinctiveness to job satisfaction of racial/ethnic minorities.
The relationships among solo status of racial/ethnic minorities in psychology departments, job satisfaction, and subjective feelings of distinctiveness were examined. Distinctiveness was defined as stigmatizing feelings associated with token status of racial/ethnic minorities in academia. It was hypothesized that minorities in positions of solo (relative to nonsolo) status within their departments, members of more stigmatized groups, and minorities occupying lower academic ranks would feel more distinctive and less satisfied with their jobs and that perceptions of distinctiveness would mediate job satisfaction. The data partially supported these hypotheses, most notably for African Americans. The implications of situational salience and the importance of recognizing differences among and between minority groups are considered.


Preparation and characterization of hemicellulose films reinforced with amino polyhedral oligomeric silsesquioxane for biodegradable packaging.
Biomass is one of the powerful alternatives to petroleum-based packaging materials. Herein, carboxymethyl hemicellulose (CMH) based films (CPF) were prepared using a convenient strategy. The chains of CMH provided the necessary supporting matrix, and the aminopropyl polyhedral oligomeric silsesquioxane (POSS-NH2) regulated the thermal and barrier properties of the CPF. The secondary amide groups and hydrogen bond were appeared in chemical structure, and SEM-EDS results indicated the preferable dispersion and compatibility of POSS-NH2 in CPFs. The thermal degradation temperature (Tonset > 260 °C), the coefficient of linear thermal expansion and glass transition temperature (Tg > 130 °C) have been improved by introduction of POSS-NH2. The tensile strength of CPF showed a higher level of 39.43 MPa with the POSS-NH2 loading of 20 wt%, which was 18.8 % higher than that of CMH film. More importantly, water vapor barrier property of films almost improved by two times, and its value is reduced to 18.82 g m-2 h-1. The shelf life of blueberry was effectively extended by the CPF coating for one week compared with commercial PE film. Therefore, CPF films displayed effective thermal performances, water vapor barrier characteristic and biodegradability, which might be exploited in packaging material for food application.


Plant-specific calmodulin-binding proteins.
Calmodulin CaM is the most prominent Ca2+ transducer in eukaryotic cells, regulating the activity of numerous proteins with diverse cellular functions. Many features of CaM and its downstream targets are similar in plants and other eukaryotes. However, plants possess a unique set of CaM-related proteins, and several unique CaM target proteins. This review discusses recent progress in identifying plant-specific CaM-binding proteins and their roles in response to biotic and abiotic stresses and development. The review also addresses aspects emerging from recent structural studies of CaM interactions with target proteins relevant to plants.


Pyridinium derivatives of histamine are potent activators of cytosolic carbonic anhydrase isoforms I, II and VII.
A series of positively-charged derivatives has been prepared by reaction of histamine with substituted pyrylium salts. These pyridinium histamine derivatives were investigated as activators of the zinc enzyme carbonic anhydrase (CA, EC 184.108.40.206) and more precisely the human isoforms hCA I, II and VII. Activities from the subnanomolar to the micromolar range were detected for these compounds as activators of the three isoforms, confirming the validity of current and previous designs. The substitution pattern at the pyridinium ring was the main factor influencing activity, the three isoforms showing different structural requirements for good activity, related with the number of pyridinium substituting groups and their nature, among various alkyl, phenyl and para-substituted styryl moieties. We were successful in identifying nanomolar potent and selective activators for each isozyme and also activators with a relatively good activity against all isozymes tested--valuable lead compounds for physiology and pathology studies involving these isozymes.


Diuresis or urinary alkalinisation for salicylate poisoning?
Forty-four adults with aspirin poisoning were treated with oral fluids only, standard forced alkaline diuresis, forced diuresis alone, or sodium bicarbonate (alkali) alone. Alkali alone was at least as effective and possibly more effective than forced alkaline diuresis in enhancing salicylate removal. Unlike the diuresis regimens it did not cause fluid retention or biochemical disturbances. The renal excretion of salicylate depends much more on urine pH than flow rate, and forced diuresis alone had little useful effect. In overdosage aspirin causes sodium and fluid retention and may impair renal function. Attempts to force a diuresis are potentially hazardous and the spurious fall in plasma salicylate concentration caused by haemodilution gives a false impression of efficacy. Further studies are required to determine the optimum treatment for salicylate poisoning.


Cavity Tightness Preferences of Overwintering Halyomorpha halys (Hemiptera: Pentatomidae).
Brown marmorated stink bug (Halyomorpha halys) (Stål) is a household nuisance pest that seeks shelter in buildings during the winter months. It has been found in a variety of cavities and spaces between building elements, as well as in the objects stored within buildings. This experiment examined the cavity tightness preferences for these insects as they settled in winter refugia. Adult overwintering H. halys were placed in two types of simulated refugia made from rigid material. Each type had a cavity of constant width, while one had a flat lid and constant tightness, and the other had a sloped lid that became tighter as insects moved inside. Adults were allowed to enter and settle, then their locations were recorded. In sloped lid cavities, H. halys tended to settle where the cavity tightness was between 4.5 and 5.5 mm. In the flat lid cavity boxes, H. halys tended to move all the way back. In both configurations, H. halys had a significant tendency to orient their heads towards the cavity entrance. A field comparison of cavity tightness in refugia with less rigid cardboard substrates was also performed, with spacers consisting of one or two layers of 3-mm cardboard. This comparison found differences in cavity selection by sex, with males more likely to pick single-spaced layers, and females more likely to select double-spaced layers. Understanding these preferences could be useful for collection, pest management, trap design, and study of impacts on structures.


Effect of backscattering in phase contrast imaging of the retina.
The observation of retinal cellular structures is fundamental to the understanding of eye pathologies. However, except for rods and cones, most of the retinal microstructures are weakly reflective and thus difficult to image with state of the art reflective optical imaging techniques such as optical coherence tomography. Recently, we demonstrated the possibility of obtaining the phase contrast of retinal cells in the eye using oblique illumination of the retina. Indeed, by illuminating the eye with incoherent oblique illumination, we obtain a secondary oblique illumination from the backscattered light which can then be used to obtain phase contrast in an effective transmission-like configuration. In this technique, a weak phase signal is modulated over an intense background. Maximizing this phase contrast is thus crucial for the image quality. Here, we investigate the parameters that affect phase contrast by modelling image formation with the backscattered light. We find that the key parameter for maximizing contrast is the intensity profile of the backscattered light. Specifically, the gradient of the profile is found to be proportional to the phase contrast. We validate the model by comparing simulations with experimental results on ex-vivo retina samples.


Changes in light absorption and composition of chromophoric marine-dissolved organic matter across a microbial bloom.
Marine chromophoric dissolved organic matter (m-CDOM) mediates many vital photochemical processes at the ocean's surface. Isolating m-CDOM within the chemical complexity of marine dissolved organic matter has remained an analytical challenge. The SeaSCAPE campaign, a large-scale mesocosm experiment, provided a unique opportunity to probe the in situ production of m-CDOM across phytoplankton and microbial blooms. Results from mass spectrometry coupled with UV-VIS spectroscopy reveal production of a chemodiverse set of compounds well-correlated with increases in absorbance after a bacterial bloom, indicative of autochthonous m-CDOM production. Notably, many of the absorbing compounds were found to be enriched in nitrogen, which may be essential to chromophore function. From these results, quinoids, porphyrins, flavones, and amide-like compounds were identified via structural analysis and may serve as important photosensitizers in the marine boundary layer. Overall, this study demonstrates a step forward in identifying and characterizing m-CDOM using temporal mesocosm data and integrated UV-VIS spectroscopy and mass spectrometry analyses.


Trivalent cation-controlled phase space of new U(IV) fluorides, Na3MU6F30 (M = Al(3+), Ga(3+), Ti(3+), V(3+), Cr(3+), Fe(3+)): mild hydrothermal synthesis including an in situ reduction step, structures, optical, and magnetic properties.
A series of new, complex U(IV) fluorides, namely, Na3MU6F30 (M = Al(3+), Ga(3+), Ti(3+), V(3+), Cr(3+), and Fe(3+)), containing trivalent transition- and main-group metal cations were synthesized via an in situ reduction step of U(VI) to U(IV). Single crystals of the series were grown in high yield under mild hydrothermal conditions and were characterized by single-crystal X-ray diffraction. The reported compounds crystallize in the trigonal space group P3̅c1 and exhibit complex crystal structures with a three-dimensional (3-D) framework composed of corner- and edge-shared UF9 polyhedra. The arrangement of U2F16 dimers forms two types of hexagonal channels, where MF6 polyhedra and sodium atoms are located. The most interesting structural feature is the presence of the 3-D framework that can accommodate various transition-metal ions in low oxidation states, indicating that the framework acts as an excellent host. Trivalent transition metal ions, even reduced Ti(3+) and V(3+), were stabilized by both the rigid framework and by our synthetic conditions. Utilizing ionic radii of transition metal ions, a phase boundary was investigated, suggesting that there exists a size limit for the M site in the crystal structure. The valence state of uranium was studied by U 4f X-ray photoelectron spectroscopy, which confirmed the presence of U(4+). Temperature-dependent magnetic susceptibility measurements yielded effective magnetic moments of 3.50 and 3.35 μB for Na3MU6F30 (M = Al(3+) and Ga(3+)), respectively. For the other compounds, combined effective magnetic moments of 8.93, 9.09, 9.18, and 10.39 μB were obtained for Ti, V, Cr, and Fe members, respectively. In all cases, large negative Weiss constants were observed, which are indicative of the existence of a spin gap in U(4+). Field-dependent magnetic property measurements at 2 K for Na3FeU6F30 demonstrated that U(4+) attains a nonmagnetic singlet ground state at low temperature. Optical and thermal properties were measured and are reported.


Tracking Foot Drop Recovery Following Lumbar-Spine Surgery, Applying Multiclass Gait Classification Using Machine Learning Techniques.
The ability to accurately perform human gait evaluation is critical for orthopedic foot and ankle surgeons in tracking the recovery process of their patients. The assessment of gait in an objective and accurate manner can lead to improvement in diagnoses, treatments, and recovery. Currently, visual inspection is the most common clinical method for evaluating the gait, but this method can be subjective and inaccurate. The aim of this study is to evaluate the foot drop condition in an accurate and clinically applicable manner. The gait data were collected from 56 patients suffering from foot drop with L5 origin gathered via a system based on inertial measurement unit sensors at different stages of surgical treatment. Various machine learning (ML) algorithms were applied to categorize the data into specific groups associated with the recovery stages. The results revealed that the random forest algorithm performed best out of the selected ML algorithms, with an overall 84.89% classification accuracy and 0.3785 mean absolute error for regression.


Regulation of surface-membrane enzymes by lipid ordering. A model based on allosteric transition theory.
This paper shows for the first time that effects of lipid ordering on the activity of surface-membrane enzymes can be interpreted in terms of the two-state allosteric transition theory. In this mathematical modelling, the conversion of an active molecule into a catalytically inactivated one of a given enzyme can be directly triggered by a change in the order parameter of lipids. Depending on the lipid order, the tendency for this conversion is either independent of the state of other enzyme molecules or co-operatively aided through intermolecular interactions that in turn depend on lipid ordering. The theory so developed is then applied to (Na+ + K+)-dependent adenosine triphosphatase (EC 188.8.131.52). On comparison of the relevant theoretical expression and published measurements, the fit to experimental results is shown to support the model. Furthermore, the model accounts for much of the data in the literature of the behaviour of this enzyme.


Prevalence of antibiotic resistance genes in subjects with successful and failing dental implants. A pilot study.
To investigate the prevalence of the bacterial genes encoding resistance to beta-lactams, tetracyclines and metronidazole respectively, in subjects with successful and failing dental implants and to assess the presence of Staphylococcus aureus and the mecA gene encoding for Methicillin Resistant Staphylococcus aureus (MRSA) in the same samples. The subject sample included 20 participants with clinically healthy osseointegrated implants and 20 participants with implants exhibiting peri-implantitis. Clinical parameters were assessed with an automated probe, samples were collected from the peri-implant sulcus or pocket and analyzed with Polymerase Chain Reaction for bla TEM , tetM, tetQ and nim genes, S. aureus and MRSA using primers and conditions previously described in the literature. Findings have shown high frequencies of detection for both groups for the tetracycline resistance genes tetM (>30%), tetQ (>65%) with no statistical differences between them (z-test with Bonferroni corrections, p<0.05). The bla TEM gene, which encodes resistance to beta-lactams, was detected in <15% of the samples. The nim gene, which encodes resistance to metronidazole, S.aureus and the mecA gene encoding for MRSA were not detected in any of the analyzed samples. Healthy peri-implant sulci and peri-implantitis cases often harbor bacterial genes encoding for resistance to the tetracyclines and less often for beta-lactams. Thus, the antimicrobial activity of the tetracyclines and to a lower extent to beta-lactams, might be compromised for treatment of peri-implantitis. Since no metronidazole resistance genes were detected in the present study, its clinical use is supported by the current findings. S.aureus may not participate in peri-implant pathology.


HLA-G functions as a restriction element and a transplantation antigen in mice.
HLA-G, a human MHC class I molecule expressed on the trophoblast during pregnancy, was expressed in transgenic mice by recombining the HLA-G gene with a transcriptional promoter from a murine H-2 MHC class I gene. Skin grafts from HLA-G transgenic mice were rejected by non-transgenic mice showing that HLA-G behaves as a xenotransplantation antigen in mice. Further investigation revealed that murine T cells recognize native HLA-G directly as a xenoantigen or they recognize processed peptides derived from HLA-G presented in the context of murine MHC molecules. HLA-G molecules also function as restriction elements capable of presenting peptides to murine T cells since immunization of HLA-G transgenic mice with peptide that binds specifically to HLA-G molecules elicited HLA-G-restricted, cytotoxic T cell responses. In addition, murine T cell responses to human xenoantigens are enhanced when responder cells originated from HLA-G transgenic mice. Based on these observations, we conclude that expression of HLA-G molecules influences selection of the murine T cell repertoire and that HLA-G exhibits immunological properties that are indistinguishable from classical HLA class I molecules when expressed in transgenic mice. Thus, any unique immunological functions mediated by HLA-G must arise from the distinctive, trophoblast-specific pattern of HLA-G expression in humans and not from structural peculiarities of HLA-G molecules.


Trigeminal neuralgia--an update.
The purpose of this article is to give a concise review of the diagnosis and management of trigeminal neuralgia (TN), with particular emphasis on idiopathic TN and symptomatic TN. The clinical characteristics of both conditions are presented, and the suspected underlying etiologies are discussed. Because it is crucial for clinicians to be able to rule out pain unrelated to TN, a list of differential diagnoses is presented. The authors stress that the diagnosis of TN is made clinically; however, diagnostic imaging may be indicated in selected cases. Current pharmacological and neurosurgical options for the management of TN are discussed in detail. In light of the popularity of unconventional treatments in the United States, the value of acupuncture and homeopathy, both of which have been suggested by some authors for the treatment of TN, is critically assessed.


Campath-1H immunosuppressive therapy reduces incidence and intensity of acute rejection in intestinal and multivisceral transplantation.
Campath-1H, an anti-CD52 antibody, is being used at our institution as immunosuppression in multivisceral and intestinal transplantation. We reviewed the pathologic findings of 1696 small bowel allograft biopsies obtained in the first 250 days posttransplant from 78 patients who underwent isolated intestinal or multivisceral transplantation and received induction immunosuppression with Campath (n = 30) or Zenapax (n = 57). We found an overall reduced incidence of acute cellular rejection (ACR) in patients receiving Campath (19.1%) compared with those on Zenapax (32.8%). The majority of Campath patients showed no rejection or was indeterminate for rejection over the period of measurement. The frequencies of mild and moderate ACR were approximately twice and three times more common, respectively, in Zenapax-treated patients. The mean grade of ACR in Campath patients compared with Zenapax patients was significantly lower (P <.01) during the first 6 weeks posttransplant. Thereafter, the grade of rejection in both patient groups showed fluctuation, with Zenapax patients sometimes having lower values (eg, at 2 to 4 months) than Campath patients. Patient and graft survival was not significantly different between the two groups. These data suggest that the incidence of ACR is significantly reduced with Campath during the first 2 months posttransplant, when compared with Zenapax. However, the incidence and intensity of ACR following this initial time period shows vacillation with both types of immunosuppression.


Statins for age-related macular degeneration.
Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the included studies. Two RCTs with 144 total participants met the selection criteria. Both trials compared simvastatin versus placebo in older people (> 50 or 60 years) with high risk of developing AMD (drusen present on examination). The larger trial with 114 participants was conducted in Australia and used a higher dose (40 mg daily) of simvastatin for three years. Participants and study personnel in this trial were adequately masked; however, data were missing for 30% of participants at three years follow-up. The smaller trial of 30 participants was conducted in Italy and used a lower dose (20 mg) of simvastatin for three months. This trial reported insufficient details to assess the risk of bias.Neither trial reported data for change in visual acuity. Analysis of 30 participants in the smaller trial did not show a statistically significant difference between the simvastatin and placebo groups in visual acuity values at three months of treatment (decimal visual acuity 0.21 ± 0.56 in simvastatin group and 0.19 ± 0.40 in placebo group) or 45 days after the completion of treatment (decimal visual acuity 0.20 ± 0.50 in simvastatin group and 0.19 ± 0.48 in placebo group). The lack of a difference in visual acuity was not explained by lens or retina status, which remained unchanged during and after the treatment period for both groups.Preliminary analyses of 42 participants who had completed 12 months follow-up in the larger trial did not show a statistically significant difference between simvastatin and the placebo groups for visual acuity, drusen score, or visual function (effect estimates and confidence intervals were not available). Complete data for these outcomes at three years follow-up were not reported. At three years, the effect of simvastatin in slowing progression of AMD compared with placebo was uncertain (odds ratio 0.51, 95% confidence interval 0.23 to 1.09).One trial did not report adverse outcomes. The second trial reported no difference between groups in terms of adverse events such as death, muscle aches, and acute hepatitis. Evidence from currently available RCTs is insufficient to conclude that statins have a role in preventing or delaying the onset or progression of AMD.


Membrane photosensitization by hematoporphyrin and hematoporphyrin derivative.
HPD-A, the putative active biologic component of HPD, photosensitized lysis of large phosphatidylcholine liposomes and lipid peroxidation in small liposomes with oxygen enhancement ratios from 4 to 5. Unambiguous proof was obtained that this damage was mediated by singlet oxygen. Spectral data indicates that HPD-A localizes in a heterogeneous environment in the large liposomes and within the membrane bilayer of the small liposomes. The latter was accompanied by a shift of the Soret band from 364 nm to 398 nm and a 2-3 fold increase of the fluorescence. The presence of human serum albumin protected the large liposomes from photosensitized damage by HPD-A and inhibited the diffusion of HPD-A into the small liposomes. In connection with photoradiation therapy, these findings suggest that aggregated HPD-A and the more fluorescent, disaggregated HPD-A may act as photodynamic sensitizers after localization, and that binding of HPD-A to serum protein protects the aggregated form and inhibits photodynamic damage to membranes. However, protein photooxidation is feasible in the protein-bound state.


In vitro assessment of thyroidal and estrogenic activities in poultry and broiler manure.
Among the many chemicals found in avian manure, endocrine disruptors (EDs), of natural or anthropogenic origin, are of special environmental concern. Nowadays, an increasing amount of estrogens is being released into the environment via the use of manure to fertilize agricultural land. While most research in this field has focused on estrogenic phenomena, little is known about alterations related to other endocrine systems, such as the thyroidal one. Here we simultaneously assessed the potential estrogenic and thyroidal activity of poultry and broiler litter manure using in vitro approaches based on estrogen receptor (Er) and thyroid receptor (Tr) transactivation assays. In addition, leaching experiments were performed to assess whether the EDs present in the manure pass through a soil column and potentially reach the groundwater. Manure from four broiler and four poultry farms was collected in two sampling campaigns carried out in two seasons (fall and spring). Extracts from broiler and poultry manure exhibited strong thyroidal activity. Only poultry manure showed estrogenic activity, which is consistent with the low levels of estrogens expected in hatchlings. Leakage experiments were performed in columns with two kinds of arable soils: sandy and loamy. No estrogenicity or thyroidal activity was detectable in soils treated with the manure or in the corresponding leachates. These results indicate that substances with estrogenic or thyroidal activity were degraded in the soil under our experimental conditions. However, the long-term effects associated with the constant and intensive application of manure to agricultural land in some regions require further research.


Generating multichain configurations of an inhomogeneous melt from the knowledge of single-chain properties.
Mean-field techniques provide a rather accurate description of single-chain conformations in spatially inhomogeneous polymer systems containing interfaces or surfaces. Intermolecular correlations, however, are not described by the mean-field approach and information about the distribution of distance between different molecules is lost. Based on the knowledge of the exact equilibrium single-chain properties in contact with solid substrates, we generate multichain configurations that serve as nearly equilibrated starting configurations for molecular dynamics simulations by utilizing the packing algorithm of [Auhl et al., J. Chem. Phys. 119, 12718 (2003)] for spatially inhomogeneous systems, i.e., a thin polymer film confined between two solid substrates. The single-chain conformations are packed into the thin film conserving the single-chain properties and simultaneously minimizing local fluctuations of the density. The extent to which enforcing incompressibility of a dense polymer liquid during the packing process is able to re-establish intermolecular correlations is investigated by monitoring intermolecular correlation functions and the structure function of density fluctuations as a function of the distance from the confining solid substrates.


The structural and electronic properties of 3,3'-azothiophene photo-switching systems.
A diversity of photo-switching structural elements opens up new opportunities in the engineering of light driven reshaping of matter, in catalysis on-click including photodynamic cancer therapy, in light sensitive transport control and in data storage. With the assistance of quantum calculations we explore the photo-physical properties of novel 3,3'-azothiophene molecular systems, the synthesis of which we reported recently. In the considered azothiophenes, upon exposure to ultraviolet and visible radiation, we observed effective anti(trans) to syn(cis) and syn(cis) to anti(trans) isomerization of the -N[double bond, length as m-dash]N- moiety, respectively. In contrast to azobenzene based photo-switchable molecular systems, the syn(cis) to anti(trans) isomerization in the azothiophenes studied does not take place at 22 °C in the dark. Temperature dependent experiments and theoretical studies suggest a slightly higher barrier for such processes than for azobenzene, which we attribute to the specific structural and electronic properties of the thiophene ring and the nature of the side groups. We discuss the potential of the observed properties in the development of novel molecular photo-switching machinery to promote biocatalytic applications at interfaces.


Association between cognitive phenotype in unaffected siblings and prospective 3- and 6-year clinical outcome in their proband affected by psychosis.
Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients. In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes ('normal', 'mixed' and 'impaired') in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype. Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype. Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.


Identification of ITPR1 gene as a novel target for hsa-miR-34b-5p in non-obstructive azoospermia: a Ca2+/apoptosis pathway cross-talk.
MiR-34b-5p has been reported as a non-invasive diagnostic biomarker for infertility. However, no gene targets regulating the mechanism of cation of this miRNA are known. In this study, using gene set enrichment analysis the Inositol 1,4,5-Trisphosphate Receptor Type 1 (ITPR1) gene was identified as the sole target for hsa-miR-34b-5p, and found significantly overexpressed in non-obstructive azoospermia (NOA) patients. This finding was confirmed by qRT-PCR on fresh testicular tissues from NOA patients. Then, pathway enrichment analysis as well as the diagnostic value analysis of hsa-miR-34b-5p/ITPR1 indicated ITPR1 as a hub gene in the calcium (Ca2+)-apoptosis pathway, and a valuable predictive biomarker for NOA. Moreover, gene expression and histological assays showed the association of the effects of ITPR1's increased expression on spermatogenesis failure through induction of apoptosis in NOA patients. These data suggested that the hsa-miR-34b-5p/ITPR1 axis could serve as a potential regulatory predictive biomarker for human spermatogenesis through the Ca2+-apoptosis pathway cross-talk.


Study on Targeting Relationship Between miR-320b and FGD5-AS1 and Its Effect on Biological Function of Osteosarcoma Cells.
To probe into the expression of FGD5-AS1 in osteosarcoma and its relationship with miR-320b. The tissue and serum samples of 97 patients with osteosarcoma were collected, and the serum samples of 100 healthy subjects who concurrently underwent physical examination were selected as the control. FGD5-AS1 expression in tissues and serum was detected, and osteosarcoma cells were transfected to measure cell behaviors such as proliferation, invasion and apoptosis. FGD5-AS1 was highly expressed in osteosarcoma, and its elevated expression indicated poor survival of patients. Serum FGD5-AS1 was related to tumor size and clinical stage and could be used for the diagnosis of osteosarcoma. The study of osteosarcoma cell lines U2OS and SaOS-2 showed that after inhibiting FGD5-AS1, the viability and invasion capacity of osteosarcoma cells decreased statistically compared with the control group (CG), while the apoptosis ability could be improved by further regulating apoptotic proteins (P<0.05). Detection of EMT-related proteins identified that E-cadherin increased while N-cadherin decreased significantly after FGD5-AS1 inhibition (P<0.05). Correlation analysis revealed a negative correlation between miR-320b and FGD5-AS1 (r = -0.410, P<0.001). Overexpression of miR-320b significantly inhibited cell viability, invasion and EMT ability, and increased the apoptosis rate, while inhibiting miR-320b expression produced the opposite results. The targeting relationship between miR-320b and FGD5-AS1 was confirmed through the biological prediction website, luciferase assay and RNA binding protein immunoprecipitation (RIP) assay. Inhibition of miR-320b could reverse the regulatory effect of FGD5-AS1 knockdown on osteosarcoma cells. FGD5-AS1 is highly expressed in osteosarcoma and is involved in the biological procession of osteosarcoma by targeting miR-320b.


ADIPOQ Gene Variants Associated with Susceptibility to Obesity and Low Serum Adiponectin Levels in Healthy Koreans.
This study aimed to measure the association between the adiponectin, C1Q and collagen domain-containing (ADIPOQ) gene variants and obesity in Koreans. Three single nucleotide polymorphisms located in the ADIPOQ gene were genotyped in a population-based cross-sectional study of 986 healthy Koreans. Three different case-control groups (i.e. G1, G2, and G3) were defined according to body mass index (BMI) and serum adiponectin levels. Allelic and genotypic associations of this gene with obesity were measured using multivariate logistic regression analyses in each group. The G allele of -11377C>G, a polymorphism located in the promoter region of the ADIPOQ gene (odds ratio (OR), 1.48; 95% confidence interval, 1.13-1.94) and most haplotypes including this allele significantly increased the risk for obesity. However, the OR decreased from 3.98 (G1 group) to 2.90 (G2 group) and 2.30 (G3 group) when a less strict definition of obesity was used. Most haplotypes, including this allele, significantly increased the risk of obesity. The statistical evidence from the GG genotype of -11377C>G (OR, 3.98) and the GT/GT diplotype composed of -11377G>C and +45T>G (OR, 5.20) confirmed the contribution of the G allele toward a predisposition for obesity. These results suggest the contribution of the ADIPOQ gene toward susceptibility to obesity in healthy Koreans. The high-risk genotypes and haplotypes identified here may provide more information for identifying individuals who are at risk of obesity.


Antibiotic management of children with infectious diseases in Dutch Primary Care.
Childhood infections are common in general practice. Although clinical guidelines recommend restrictive antibiotic use for children, antibiotics are too often prescribed. The aim of this study was to obtain insight in antibiotic prescribing for children related to clinical diagnoses. This is pivotal to define improvement strategies in the antibiotic management. In this observational study, we used consultation data collected from 45 general practices in the Netherlands in 2012. Infectious disease episode incidences, the number of antibiotic prescriptions per 1000 person-years, the proportion of episodes with an antibiotic prescription and the choice of antibiotic subclass were analysed for the most relevant diagnoses over different ages. A total of 262 antibiotic courses were prescribed per 1000 person-years on average, with the highest number among children of 1 year (714/1000 person-years). Antibiotics were prescribed in 24% of infectious disease episodes. Acute upper respiratory tract infection (RTI) was the most common reason to visit the GP (173/1000 person-years), and the second most frequent indication to prescribe antibiotics. Antibiotics were most often prescribed for acute otitis media (58/1000 person-years). Amoxicillin dominated prescribing (55%), followed by macrolides (14%) and amoxicillin/clavulanate (10%), prescribing of narrow-spectrum antibiotics was low (10%). This detailed insight in antibiotic management of childhood infections shows targets for Dutch improvement strategies: (i) prevent antibiotic prescribing for acute upper RTI and bronchitis; (ii) stimulate the use of narrow-spectrum antibiotics; and (iii) reduce the use of macrolides and amoxicillin/clavulanate. Furthermore, this information is helpful to compare antibiotic policy between countries.


Assessing food additive toxicity using a cell model.
Food additives are widely used for technological purposes and their presence is often substantial daily diet. They have also been accused forvarious toxic reactions in humans. The toxicity of the food color tartrazine, the preservatives sodium nitrate and sodium benzoate, and the antioxidant BHT, was studied using the protozoan Tetrahymenapyriformis as a toxicological model. The 4 food additives were added to Tetrahymena cultures and DNA content of the protozoan nuclei measured by an image analysis system. These food additives caused a statistically significant increase in DNA content suggesting stimulation of the mitotic process. This system may contribute to the investigation of the cellular action of food additives, since mitogenic stimuli substantially alter susceptibility to chemical carcinogenesis.


[Vitaflon vascular graft for portocaval shunt: experimental and clinical study].
Native "Vitaflon" vascular graft made of spongeous polytetrafluoroethylene for portocaval shunt was evaluated in patients with portal hypertension. Experimental series in grey rabbits proved high biological inertness of the graft. It was used for portocaval shunt in 13 patients. The follow-up from 1 to 32 months demonstrated successful results in 12 cases.


The proteins of Murray Valley encephalitis virus.
Proteins specified by Murray Valley encephalitis virus were labelled during virus growth in Vero and in PS cells, and separated by polyacrylamide gel electrophoresis. The purified virus particle contains three proteins (V-1, V-2 AND V-3) whereas the slow sedimenting haemagglutinin or virus sub-particle lacks the core protein V-2 but contains NV-2, a non-structural protein. Seven non-structural proteins in addition to V-2 and V-3 were identified in infected cells. Electrophoretic profiles by virus-specified proteins in both cell lines were almost identical after elimination by a double-label technique of the background of continuing host-cell protein synthesis. Glucosamine was incorporated into the envelope protein V-3 and NV-2. From 26 to 46h post-infection in Vero cells, the proportion and amounts of virus-specified proteins remained constant and they were non-equimolar; incorporation of labelled leucine into V-2 was much greater than incorporation into NV-2, whereas in cells infected with Kunjin (a related flavivirus) this ratio of incorporation was reversed. At 21 to 25h, the synthesis of V-2 was less prominent but there was an enhanced synthesis of NV-X. Apart from V-I, NV-I, NV-4 and NV-5, all proteins are larger than the corresponding Kunjin virus proteins and together represent about 400 x 10-3 daltons of polypeptide synthesis, which is close to the maximum coding content of the flavivirus genome.


Loss of p53 protein in human papillomavirus type 16 E6-immortalized human mammary epithelial cells.
We have shown previously that introduction of the human papillomavirus type 16 (HPV16) or HPV18 genome into human mammary epithelial cells induces their immortalization. These immortalized cells have reduced growth factor requirements. We report here that transfection with a single HPV16 gene E6 is sufficient to immortalize these cells and reduce their growth factor requirements. The RB protein is normal in these cells, but the p53 protein is sharply reduced, as shown by immunoprecipitation with anti-p53 antibody (pAB 421). We infer that the E6 protein reduces the p53 protein perhaps by signalling its destruction by the ubiquitin system. The HPV-transforming gene E7 was unable to immortalize human mammary epithelial cells. Thus, cell-specific factors may determine which viral oncogene plays a major role in oncogenesis.


Strategies to overcome obstacles to successful immunotherapy of melanoma.
The immunogenicity of malignant melanomas has been recognized by the observed recruitment of tumor-specific cytotoxic T-cells (CTL), leading to the identification of several melanoma associated antigen (MAA). However, numerous strategies to treat melanoma with immunotherapy have resulted in only partial success. In this editorial, we discuss recent data related to the ability of tumors to elude immune responses. We therefore discuss different strategies to induce a clinically effective immune response. These approaches include 1) immunostimulation: including peptide/protein based vaccines, dendritic cell vaccines, and adoptive cell transfer; and 2) overcoming immunosuppression, including targeting of checkpoint molecules such as CTLA-4, circumventing the activity of Tregs, and assuring antigen expression by tumor cells (thwarting antigen silencing). Finally, we discuss recent advances in gene therapy, including adoptive therapy with engineered T cell receptors (TCRs). These issues lead to the conclusion that successful immunotherapy in malignant melanoma requires a combination of strategies aimed at both inducing immunostimulation and blocking immunosuppression.


Neuroplasticity of edentulous patients with implant-supported full dentures.
Edentulous patients with implant-supported prostheses report improved tactile discriminative capabilities and motor function compared with when they wore complete dentures. 'Osseoperception' is defined as the ability to identify kinesthetic sensation without the input from periodontal mechanoreceptors. This sensation is generated from the temporomandibular joint, masticatory muscle, mucosa, and periosteum, and provides sensory and motor information related to mandible movements and occlusion. The aim of this study was to analyze the cortical plasticity occurring in patients with implant-supported prostheses. Twenty edentulous patients with implant-supported full dentures or traditional complete dentures were recruited for a clenching task. They were scanned by functional magnetic resonance imaging (fMRI), and the data were analyzed using the spm99 software package to generate activation brain maps. Increased blood oxygen level dependent signals in the primary sensorimotor cortex were found in patients with implant-supported fixed dentures. Other activated areas included prefrontal cortex, Broca's area, premotor cortex, supplementary motor area, superior temporal gyrus, insular, basal ganglion, and hippocampus. We suggest that sensory and motor feedback to the central nervous system can be restored by implant-supported full dentures. Activation of the primary sensorimotor cortex in patients with implant-supported dentures might explain the improved tactile, stereognostic ability, and mastication functions, which are more similar to the natural dentition.


Non-human predator interactions with wild great apes in Africa and the use of camera traps to study their dynamics.
The slow life histories of great apes (hereafter 'apes') combined with a growing inventory of predation incidents suggest that apes may be strongly affected by direct predation, as well as by predation risk. Predation risk may shape and increase behavioural flexibility by forcing individuals to adapt their behaviour to predator patterns. Forest leopards are an apex predator of primates in African rain forests and may represent a significant risk to ape populations. More field data are needed to further elucidate the behavioural modifications of apes in response to predation. We present research methods that combine the use of remote camera traps, capture-mark-recapture statistics and occupancy modelling to study predator-African ape relationships and potential antipredator behaviour through spatial variation in species co-occurrence patterns.


Behaviour of silica nanoparticles in dermis-like cellularized collagen hydrogels.
A model of the fate of colloidal silica in the dermis was designed based on the diffusion of fluorescent silica nanoparticles through collagen hydrogels. The diffusion process was found to depend on particle size (10-200 nm) and surface charge, as well as on collagen concentration (1.5-5 mg mL-1). The presence of human dermal fibroblasts within the hydrogels also significantly impacted on the behaviour of the particles. In particular, the simultaneous monitoring of particulate and soluble forms of silica showed that both the hydrogel network and the cellular activity have a strong influence on the solubilization process of the silica particles, through a combination of surface sorption, uptake and intracellular dissolution. Interactions between silica and collagen in 3D environments also lower the cytotoxicity of 10 nm particles compared to traditional 2D cultures. The results emphasize the complexity of silica chemistry in living tissues and specifically indicate the need for further investigations of the in vivo behaviour of its soluble forms.


Green space quality and adolescent mental health: do personality traits matter?
Adolescents, especially females, tend to experience poorer mental health if they are higher in introversion and neuroticism. As a result, they also may have more to gain from having quality green space (e.g. parks) nearby to enable restoration, but this remains tested. Cross-sectional data on 2946 adolescents aged 16-17y were extracted from the Longitudinal Study of Australian Children. Multilevel linear regressions assessed association between parent/caregiver green space quality perception with self-reported Strengths and Difficulties Questionnaire Total Difficulties Scores (TDS) and internalising (e.g. anxiety) and externalising (e.g. fidgetiness) subscales. Models were weighted for representativeness, accounted for spatial clustering within postcodes, and adjusted for geographic stratum and socioeconomic confounders. This was followed by adjustment for introversion and neuroticism, and then three-way interaction terms between each trait, green space quality and sex to assess for potential effect modification. Quality green spaces was associated with higher TDS (β = 1.506; SE = 0.371), internalising (β = 0.982; SE = 0.220) and externalising (β = 0.518; SE = 0.234) scores (i.e. poorer mental health). Introversion was associated with higher TDS (β = 1.416; SE = 0.089), higher internalising (β = 1.233; SE = 0.050) and higher externalising scores (β = 0.181; SE = 0.056). Similar associations were observed for neuroticism and TDS (β = 2.283; SE = 0.084), internalising (β = 1.627; SE = 0.046) and externalising scores (β = 0.656; SE = 0.056). Mean levels of introversion were similar for girls and boys (1.73 vs 1.76, p = 0.6573), but mean levels of neuroticism were notably higher in girls than boys (2.42 and 1.67, p < 0.0001). Likelihood ratio tests indicated three-way interactions improved models analysing the internalising subscale outcome only. Green space quality made no difference to associations between introversion or neuroticism and internalising scores in males. Quality green space was associated with 3.2 and 2.1 reductions in mean internalising scores among females with the highest levels of introversion or neuroticism, respectively. Individual differences in psychological traits may predispose some adolescents, and females especially, to restoration from green space.


Hemophagocytic lymphohistiocytosis in a patient with Goodpasture's syndrome: a rare clinical association.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome. HLH can occur in the setting of an autoimmune disease, chronic immunosuppression, malignancy, and infection. We discuss a rare case of a young woman who was diagnosed with Goodpasture's syndrome that was most likely complicated by HLH. To the best of our knowledge, this is the first report of HLH in the setting of this rare autoimmune disease. A 31-year-old woman who was diagnosed with Goodpasture's syndrome 7 years prior presented with febrile neutropenia. She was initially receiving treatment with azathioprine and prednisone, which was subsequently switched to hydroxychloroquine. Over time, she had developed polyarthritis and was later diagnosed with MPO-ANCA-positive vasculitides. On this admission, her clinical status deteriorated from persistent pancytopenia. This was initially attributed to the immunosuppressive effect of hydroxychloroquine. A bone marrow biopsy was performed and revealed hypercellular bone marrow without any cytogenetic abnormalities. Due to a prolonged pancytopenia thought to be of autoimmune etiology, treatment with high-dose steroids was initiated. With the persistent febrile episodes, hepatosplenomegaly on examination, and laboratory workup that revealed hyperferritinemia and pancytopenia, HLH syndrome was suspected. A repeat bone marrow biopsy confirmed this diagnosis with the presence of hemophagocytosis, demonstrated by the presence of histiocytes engulfing erythroid cells. She also met 5 of 8 diagnostic criteria, which confirmed the diagnosis of HLH. The patient eventually died despite aggressive treatment with high-dose steroid therapy for her autoimmune disorder, as well intravenous antibiotics and supportive care for her underlying infections. HLH is a syndrome marked by a hyper-inflammatory state aggravated by specific triggers. To make the diagnosis of HLH, at least 5 of the 8 criteria must be met. Treatment involves suppression of the overwhelming inflammatory response by the use of immunomodulators. The mortality rate can range from 50-90% due to delayed recognition and onset of treatment. Here, we present a rare case of Goodpasture's syndrome with overlap and pauci-immune vasculitis, which may have triggered the HLH. This correlation has not been described before in the literature.


Outbreak of Mycobacterium bovis infection in a wild animal park.
An outbreak of tuberculosis due to Mycobacterium bovis occurred in a wild animal park. Three pot-bellied pigs (Sus scrofa vittatus), one red deer (Cervus elaphus), one buffalo (Bison bonasus) and two European lynxes (Lynx lynx) were affected and showed clinical signs including weight loss, enlarged lymph nodes and paralysis of the hindlimbs. Postmortem examinations revealed multifocal granulomatous lesions in various organs, including the lymph nodes, lungs, intestines, kidneys and the central nervous system. Acid-fast organisms were demonstrated in various organs histologically and bacteriologically. Spoligotyping of 17 isolates from various organs of the affected animals confirmed an infection by M bovis and revealed an identical pattern indicating a common origin. The spoligotype was different from the pattern of M bovis recorded in the cattle population in Germany between 2000 and 2006. Investigations of sentinel animals such as an aged silver fox (Vulpes vulpes), a badger (Meles meles), a ferret (Mustela putorius) and rodents, and tuberculin skin tests of the animal attendants and randomly collected faecal samples from the enclosures were all negative for M bovis.


Bacterial adherence to intravenous catheters and needles and its influence by cannula type and bacterial surface hydrophobicity.
Bacterial adherence to intravenous (IV) catheters and needles (cannulas) was studied morphologically by scanning electron microscopy and determined quantitatively with radiolabeled bacteria. Electron micrographs showed that bacteria adhered well to IV cannulas with formation of microcolonies. The adherence process was studied quantitatively, as related to cannula composition and bacterial surface hydrophobicity. The adherence of the bacteria examined (per square centimeter) was lowest to siliconized steel needles, higher to Teflon catheters, and highest to polyethylene catheters. The results for Staphylococcus aureus were (9.9 +/- 0.9) X 10(5) bacteria/cm2 adhered to steel needles, (37.2 +/- 2.8) X 10(5) bacteria/cm2 to Teflon catheters, and (168.4 +/- 15.6) X 10(5) bacteria/cm2 to polyethylene catheters. Hydrophobic bacteria (S. aureus and Serratia marcescens), as determined by their adherence to liquid hydrocarbons, adhered better than less hydrophobic species (Escherichia coli). The role of hydrophobicity was documented by showing that hydrophobic S. marcescens adhered to IV catheters 18- to 27-fold better than its less hydrophobic mutants. It is concluded that IV steel needles have an advantage over plastic cannulas regarding bacterial adherence in vitro, and inasmuch as infectious complications in vivo were indeed shown to be lower with IV needles, their usage should be preferred.


Recurrent mesectodermal leiomyoma of the ciliary body: a case report.
A 19-yr-old woman with a previous history of a mass of the right ciliary body presented with a decreased visual acuity of right eye. Clinicoradiologic examinations suggested a recurrent mass of the ciliary body. Enucleation of the right eye was performed under the impression of malignant tumor. On microscopic examination, the tumor was a mesectodermal leiomyoma of the ciliary body. On immunohistochemistry, the tumor cells were reactive to smooth muscle actin and vimentin, but not reactive to cytokeratin, S-100 protein, neurofilament, desmin, epithelial membrane antigen, HMB-45, glial fibrillary acidic protein, and synaptophysin. Electron microscopy revealed numerous thin longitudinally placed myofilaments and focal densities in the cytoplasms. In the review of the literature, only 27 cases of mesectodermal leiomyoma of the ciliary body were reported, however, there was no report of recurrent cases. Mesectodermal leiomyoma should be differentiated from other orbital spindle-cell tumors such as amelanotic melanomas and glial tumors. Immunohistochemical and electron microscopic studies may be useful for the correct diagnosis by showing smooth muscle differentiation in the tumor cells.


Montelukast Prevents Mice Against Acetaminophen-Induced Liver Injury.
Acetaminophen (APAP) is a widely used over-the-counter antipyretic and analgesic drug. Overdose of APAP is the leading cause of hospital admission for acute liver failure. Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (Cysltr1), which protects from inflammation and oxidative stress. However, the function of montelukast in APAP-induced hepatotoxicity remains unknown. In this study, we examined whether pharmacological inhibition of Cystlr1 could protect mice against APAP-induced hepatic damage. We found that APAP treatment upregulated messenger RNA and protein levels of Cysltr1 both in vitro and in vivo. Pharmacological inhibition of Cysltr1 by montelukast ameliorated APAP-induced acute liver failure. The hepatoprotective effect of montelukast was associated with upregulation of hepatic glutathione/glutathione disulfide level, reduction in c-Jun-NH2-terminal kinase activation and oxidative stress. In mouse primary hepatocytes, inhibition of Cysltr1 by montelukast ameliorated the expression of inflammatory-related genes and APAP-induced cytotoxicity. We conclude that montelukast may be used to treat APAP-induced acute hepatic injury.


The effect of mindfulness meditation training on biological acute stress responses in generalized anxiety disorder.
Mindfulness-Based interventions have increased in popularity in psychiatry, but the impact of these treatments on disorder-relevant biomarkers would greatly enhance efficacy and mechanistic evidence. If Generalized Anxiety Disorder (GAD) is successfully treated, relevant biomarkers should change, supporting the impact of treatment and suggesting improved resilience to stress. Seventy adults with GAD were randomized to receive either Mindfulness-Based Stress Reduction (MBSR) or an attention control class; before and after, they underwent the Trier Social Stress Test (TSST). Area-Under-the-Curve (AUC) concentrations were calculated for adrenocorticotropic hormone (ACTH) and pro-inflammatory cytokines. MBSR participants had a significantly greater reduction in ACTH AUC compared to control participants. Similarly, the MBSR group had a greater reduction in inflammatory cytokines' AUC concentrations. We found larger reductions in stress markers for patients with GAD in the MBSR class compared to control; this provides the first combined hormonal and immunological evidence that MBSR may enhance resilience to stress.


A cervical abnormality risk prediction model: can we use clinical information to predict which patients with ASCUS/LSIL Pap tests will develop CIN 2/3 or AIS?
Human papillomavirus (HPV) infections and abnormal Pap test results are common, and most do not progress to cervical cancer. Because it is difficult to predict which mild Pap abnormalities will develop into precancerous lesions, many women undergo painful and costly evaluations and even unnecessary treatment. The objective of this study was to develop a risk prediction model based on clinical and demographic information to identify women most likely to develop significant precancerous lesions (cervical intraepithelial neoplasia grades 2/3 [CIN 2/3] or adenocarcinoma in situ [AIS]) among women with mild Pap abnormalities (atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion). The Abnormal Pap Smear Registry includes women who received treatment at the Brigham and Women's Hospital/Dana Farber Cancer Institute Pap Smear Evaluation Center beginning in 2006. It includes 1,072 women with mild cervical dysplasia (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion) on their referral Pap test. We derived a clinical prediction model to predict the probability of developing CIN 2/3 or AIS using multivariate logistic regression with a split-sample approach. By the end of the follow-up, 93 of the 1,072 women developed CIN 2/3 or AIS (8.7%). There were several differences between women who developed CIN 2/3 or AIS and women who did not. However, once we put these into the regression model, the only variable that was significantly associated with CIN 2/3 or AIS was having a history of an abnormal Pap or biopsy result (odds ratio = 2.44; 95% CI =1.03-5.76). The resulting prediction model had poor discriminative ability and was poorly calibrated. Despite accounting for known risk factors, we were unable to predict individual patients' probability for progression on the basis of available data.


Immune Checkpoint Inhibitors in Triple Negative Breast Cancer Treatment: Promising Future Prospects.
Immunotherapy has emerged as the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy, and targeted therapy. Immune checkpoint inhibitors are the current superheroes of immunotherapy, unleashing a patient's own immune cells to kill tumors and revolutionizing cancer treatment in a variety of cancers. Although breast cancer was historically believed to be immunologically silent, treatment with immune checkpoint inhibitors has been shown to induce modest responses in metastatic breast cancer. Given the inherent heterogeneity of breast tumors, this raised the question whether certain breast tumors might benefit more from immune-based interventions and which cancer cell-intrinsic and/or microenvironmental factors define the likelihood of inducing a potent and durable anti-tumor immune response. In this review, we will focus on triple negative breast cancer as immunogenic breast cancer subtype, and specifically discuss the relevance of tumor mutational burden, the plethora and diversity of tumor infiltrating immune cells in addition to the immunoscore, the presence of immune checkpoint expression, and the microbiome in defining immune checkpoint blockade response. We will highlight the current immune checkpoint inhibitor treatment options, either as monotherapy or in combination with standard-of-care treatment modalities such as chemotherapy and targeted therapy. In addition, we will look into the potential of immunotherapy-based combination strategies using immune checkpoint inhibitors to enhance both innate and adaptive immune responses, or to establish a more immune favorable environment for cancer vaccines. Finally, the review will address the need for unambiguous predictive biomarkers as one of the main challenges of immune checkpoint blockade. To conclude, the potential of immune checkpoint blockade for triple negative breast cancer treatment could be enhanced by exploration of aforementioned factors and treatment strategies thereby providing promising future prospects.


Strengthening health systems through HIV monitoring and evaluation in Sub-Saharan Africa.
In this review, we describe the challenges faced by using clinical cohorts to perform Monitoring and Evaluation (M&E) and the possible solutions for increasing and strengthening health systems in low-income and middle-income countries. HIV scale-up has facilitated the transition from paper-based medical records to electronic medical records at hundreds of sites in most of the countries in sub-Saharan Africa and the implementation of national HIV databases. However, National M&E systems in resource-limited settings tend to be chronically challenged by persistently incomplete reporting and inaccurate data, which undermines their usefulness. In low-income and middle-income countries, new information technologies such as Web-based systems and mobile phone networks are expanding rapidly. Their use will improve data quality and, therefore, reduce participant dropout and improve reporting rates. These systems have the potential to allow real time access to summary reports and to integrate data from other settings such as maternal and infant health clinics. The efforts to address the AIDS pandemic in sub-Saharan Africa will require enhanced information systems. Stronger systems are needed to deliver primary healthcare for those with and without HIV, and it is also essential to build and take advantage of synergies across health information systems.


Oscillation induced by Hopf bifurcation in the p53-Mdm2 feedback module.
This study develops an integrated model of the p53-Mdm2 interaction composed of five basic components and time delay in the DNA damage response based on the existing research work. Some critical factors, including time delay, system parameters, and their interactions in the p53-Mdm2 system are investigated to examine their effects on the oscillatory behaviour induced by Hopf bifurcation. It is shown that the positive feedback formed between p53 and the activity of Mdm2 in the cytoplasm can cause a slight decrease in the amplitude of the p53 oscillation. The length of the time delay plays an important role in determining the amplitude and period of the oscillation and can significantly extend the parameter range for the system to demonstrate oscillatory behaviour. The numerical simulation results are found to be in good agreement with the published experimental observation. It is expected that the results of this research would be helpful to better understand the biological functions of p53 pathway and provide some clues in the treatment of cancer.


Polydopamine modification of silk fibroin membranes significantly promotes their wound healing effect.
Natural polymer-based wound dressings have gained great attention in skin tissue engineering. Silk fibroin (SF) spun from Bombyx mori (B. mori) is a potential wound dressing material due to its outstanding biocompatibility and biodegradability, however, its wound healing effect is still limited. To maximize the wound healing effect of SF-based wound dressing, we first fabricated fibrous electrospun SF (ESF) membranes with large porosity and specific surface area, and then formed polydopamine (PDA) coating on the ESF fibers to form PESF membranes. We found that PDA coating enabled the PESF membranes to outperform the ESF membranes in enhancing the hydrophilicity and protein adsorption ability of the membranes as well as the attachment, spreading and proliferation of fibroblasts on the membranes in vitro. Our further in vivo histological analysis confirmed that the PESF membranes accelerated wound healing in a rat skin wound model more effectively within 2 weeks than both the ESF membrane and a commercial dressing (3M™ Tegaderm™). The enhanced wound healing effect of the PESF membranes was further proved by the increase in the content of hydroxyproline (a constituent in collagen) in the wound treated by the PESF membranes. Therefore, the PESF membranes could be used as a promising wound dressing for wound healing and skin regeneration.


Unusual cause of filling defect in pulmonary artery: pulmonary artery sarcoma.
Pulmonary artery (PA) sarcoma is an extremely rare malignant tumor of pulmonary artery. It is often misdiagnosed as pulmonary thromboembolism (PTE) because of its clinical and imaging features which are quite similar to PTE. Multimodality diagnostic imaging and recognition of specific imaging characteristics with appropriate clinical suspicion are required to make correct diagnosis. In this report, we present a case of PA sarcoma with imaging and clinical features as well as emphasize significance of using multimodality imaging.


Characterizing Bone Phenotypes Related to Skeletal Fragility Using Advanced Medical Imaging.
Summarize the recent literature that investigates how advanced medical imaging has contributed to our understanding of skeletal phenotypes and fracture risk across the lifespan. Characterization of bone phenotypes on the macro-scale using advanced imaging has shown that while wide bones are generally stronger than narrow bones, they may be more susceptible to age-related declines in bone strength. On the micro-scale, HR-pQCT has been used to identify bone microarchitecture phenotypes that improve stratification of fracture risk based on phenotype-specific risk factors. Adolescence is a key phase for bone development, with distinct sex-specific growth patterns and significant within-sex bone property variability. However, longitudinal studies are needed to evaluate how early skeletal growth impacts adult bone phenotypes and fracture risk. Metabolic and rare bone diseases amplify fracture risk, but the interplay between bone phenotypes and disease remains unclear. Although bone phenotyping is a promising approach to improve fracture risk assessment, the clinical availability of advanced imaging is still limited. Consequently, alternative strategies for assessing and managing fracture risk include vertebral fracture assessment from clinically available medical imaging modalities/techniques or from fracture risk assessment tools based on clinical risk factors. Bone fragility is not solely determined by its density but by a combination of bone geometry, distribution of bone mass, microarchitecture, and the intrinsic material properties of bone tissue. As such, different individuals can exhibit distinct bone phenotypes, which may predispose them to be more vulnerable or resilient to certain perturbations that influence bone strength.


Platelet derived growth factor receptor alpha is essential for establishing a microenvironment that supports definitive erythropoiesis.
The hematopoietic system undergoes a qualitative change during the embryogenesis of most vertebrates. It is designated as the shift of primitive to definitive hematopoiesis and suitable microenvironment must be established to support this shift. While studying the role of platelet derived growth factor receptor alpha (PDGFR alpha) in embryonic hematopoiesis, we found that it was expressed in a stromal cell component of liver, a major site of this shift, but not in the yolk sac, the site of primitive hematopoiesis. Thus, we considered that development of PDGFRalpha positive stromal cells is an essential requirement for this shift. Without PDFGRalpha positive cell component, erythropoiesis was suppressed in the culture of fetal liver. Moreover, injection of an antagonistic anti-PDGFRalpha monoclonal antibody during embryogenesis suppressed the production of definitive erythrocytes. These indicated that PDGF exerts its effect on a subset of stromal components to prepare a microenvironment that can support the definitive erythropoiesis.


The difference between cytokeratin 20 expression in high- and low-grade urothelial bladder carcinomas: A cross-sectional study.
Bladder cancer is one of the most common cancers worldwide. Expression of cytokeratin 20 (CK 20) could be used as a biomarker in different epithelia to determine malignancy, especially in gastrointestinal, urinary tract, and Merkel cells. CK 20 could be detected in several urothelial carcinomas and was associated with bladder cancer recurrence. The study aimed to assess the utility of CK 20 expression for bladder cancer grading. This was a retrospective study assessing CK 20 expression in 73 bladder cancer patients who had transurethral resection of bladder tumor or cystectomy. The data were then collected and analyzed with SPSS Statistics version 20.0. Fifty-six (76.7%) cases of high- and 17 (23.3%) cases of low-grade urothelial bladder cancer were examined for CK 20 expression. Positive expression was present in 57 (78.1%) samples. A significant difference (P = 0.034) in CK 20 expression was observed between low-grade and high-grade urothelial carcinomas. Positive expression was seen in 44 (77.2%) high-grade cases and only 13 (22.8%) low-grade cases. The difference in the CK 20 expression was found to be statistically significant among different grades of bladder cancer but not to metastatic bladder cancer. Further, studies are required to establish CK 20 as a diagnostic tool. We suggest a combination with several markers to compare which is superior.


First Genome of Labyrinthula sp., an Opportunistic Seagrass Pathogen, Reveals Novel Insight into Marine Protist Phylogeny, Ecology and CAZyme Cell-Wall Degradation.
Labyrinthula spp. are saprobic, marine protists that also act as opportunistic pathogens and are the causative agents of seagrass wasting disease (SWD). Despite the threat of local- and large-scale SWD outbreaks, there are currently gaps in our understanding of the drivers of SWD, particularly surrounding Labyrinthula spp. virulence and ecology. Given these uncertainties, we investigated the Labyrinthula genus from a novel genomic perspective by presenting the first draft genome and predicted proteome of a pathogenic isolate Labyrinthula SR_Ha_C, generated from a hybrid assembly of Nanopore and Illumina sequences. Phylogenetic and cross-phyla comparisons revealed insights into the evolutionary history of Stramenopiles. Genome annotation showed evidence of glideosome-type machinery and an apicoplast protein typically found in protist pathogens and parasites. Proteins involved in Labyrinthula SR_Ha_C's actin-myosin mode of transport, as well as carbohydrate degradation were also prevalent. Further, CAZyme functional predictions revealed a repertoire of enzymes involved in breakdown of cell-wall and carbohydrate storage compounds common to seagrasses. The relatively low number of CAZymes annotated from the genome of Labyrinthula SR_Ha_C compared to other Labyrinthulea species may reflect the conservative annotation parameters, a specialized substrate affinity and the scarcity of characterized protist enzymes. Inherently, there is high probability for finding both unique and novel enzymes from Labyrinthula spp. This study provides resources for further exploration of Labyrinthula spp. ecology and evolution, and will hopefully be the catalyst for new hypothesis-driven SWD research revealing more details of molecular interactions between the Labyrinthula genus and its host substrate.


Intrapulmonary BCG cell wall vaccination in mice.
Mice of two inbred strains, Balb/c and C3H/He, were given three dosages of mycobacterium bovis BCG (5 X 10(4), 5 X 10(2) and 5 colony forming units) by either the intravenous route or by a direct intratracheal (non-aerosol) route. The magnitude of the infectivity of these inoculae given by these routes was assessed by measurement of weight changes and mycobacterial multiplication in the spleen and lung. As expected, the Balb/c strain was more susceptible to infection than the C3H/He strain. However, for both strains, infection by the intratracheal route resulted in mycobacterial counts in the lungs which were more than seven-fold higher than mycobacterial counts after intravenous challenge. Naive Balb/c mice were immunized with BCG cell wall vaccine by the intratracheal route, by the intravenous route or by subcutaneous immunization. Four weeks later mice were challenged with live BCG by the intratracheal route. Following challenge, mycobacterial counts in the lungs of mice immunized by the intratracheal route, but not in the lungs of the mice immunized by the intravenous and subcutaneous routes, were significantly lower compared to controls. These results suggest that immunization with killed BCG by the intratracheal route imparts more effective mycobacterial intrapulmonary immunity than immunization by systemic routes.


The clinical experience with levosimendan in anesthesiology and in the intensive care unit.
In the present review striking data showing that intensive care unit patients with acute heart failure and high-risk surgical patients may markedly benefit from the use of levosimendan are presented. Indeed, levosimendan is an effective new agent that acts via two complementary mechanisms. It enhances cardiac contractility by improving the response of the myofilaments to intracellular calcium, and it reduces the cardiac workload by opening the adenosine triphosphate-dependent potassium channels for the dilation of blood vessels. Because the therapeutic levels of levosimendan do not increase the intracellular calcium concentrations, levosimendan is less likely than traditional inotropes (beta-agonist inotropes or phosphodiesterase inhibitors) to elicit arrhythmias or impair diastolic relaxation. In fact, the results of recent clinical studies indicate that levosimendan offers significant hemodynamic and survival benefits when given to patients who are hospitalized for acute heart failure. Indeed, in the near future, it is likely that levosimendan may also prove effective for the treatment of patients with diastolic heart failure or for those with a low cardiac output following coronary artery bypass grafting. In addition, levosimendan has the potential of supporting the cardiac function during the initiation of beta-blocker therapy, for weaning patients from cardiopulmonary bypass, for individuals with valvular abnormalities and for those with myocarditis. Preliminary results also suggest that levosimendan may be beneficial for the treatment of patients with right ventricular heart failure. Although the use of levosimendan has been fully validated for the most common causes of acute heart failure, additional clinical trials are needed to safety broaden its therapeutic indications.


Impact of achilles tendon lengthening on functional limitations and perceived disability in people with a neuropathic plantar ulcer.
An Achilles tendon-lengthening (ATL) procedure is effective at reducing ulcer recurrence in patients with diabetes, peripheral neuropathy, and a plantar ulcer, but its effects on functional limitations and perceived disability are unknown. The purpose of this study is to report the effects of an ATL and total contact casting (TCC) on the functional limitations and perceived disability of patients with neuropathic plantar ulcers. Twenty-eight subjects with a mean age of 55 +/- 10 years and a BMI of 33 +/- 6 kg/m(2) participated. All subjects had a history of diabetes, loss of protective sensation, limited ankle motion, and a recurrent forefoot ulcer. Subjects were randomized into two groups: an ATL group (n = 14), who received treatment of ATL, and TCC and a TCC group (n = 14), who received TCC only. Subjects completed a modified physical performance test (PPT) and the SF-36 Health Survey before treatment, after primary treatment and healing of the plantar forefoot ulcer, and 8 months after initial ulcer healing. There were no significant changes in functional limitations as measured by the PPT between groups or over time. The physical summary score of the SF-36 decreased slightly from before treatment to 8 months after initial ulcer healing in the ATL group (35 +/- 7 to 31 +/- 6), whereas the TCC group score increased during this time (34 +/- 8 to 39 +/- 11; P < 0.05). The ATL resulted in no measurable change in functional limitations, but patients receiving an ATL and TCC reported lower physical functioning at 8 months after initial ulcer healing than subjects receiving TCC alone and may require additional physical therapy to address this perceived disability.


Effects of increased intracranial pressure on cerebral blood volume, blood flow, and oxygen utilization in monkeys.
The relationship of cerebral blood volume (CBV) to cerebral perfusion pressure (CPP), cerebral blood flow (CBF), and the cerebral metabolic rate for oxygen (CMRO2) was examined in rhesus monkeys. In vivo tracer methods employing radioactive oxygen-15 were used to measure CBV, CBF, and CMRO2. Cerebral perfusion pressure was decreased by raising the intracranial pressure (ICP) by infusion of artificial cerebrospinal fluid (CSF) into the cisterna magna. The production of progressive intracranial hypertension to an ICP of 70 torr (CPP of 40 torr) caused a rise in CBV accompanied by a steady CBF. With a further increase in ICP to 94 torr, CBV remained elevated without change while CBF declined significantly. Cerebral metabolic rate for oxygen did not change significantly during intracranial hypertension. For comparison, CPP was lowered by reducing mean arterial blood pressure in a second group of monkeys. Only CBF was measured in this group. In this second group of animals, the lower limit of CBF autoregulation was reached at a higher CPP (CPP approximately to 80 torr) than when an increase in ICP was employed (CPP approximately to 30 torr).


Endoscopic ultrasound in chronic pancreatitis: where are we now?
Endoscopic ultrasonography (EUS) is well suited for assessment of the pancreas due to its high resolution and the proximity of the transducer to the pancreas, avoiding air in the gut. Evaluation of chronic pancreatitis (CP) was an early target for EUS, initially just for diagnosis but later for therapeutic purposes. The diagnosis of CP is still accomplished using the standard scoring based on nine criteria, all considered to be of equal value. For diagnosis of any CP, at least three or four criteria must be fulfilled, but for diagnosis of severe CP at least six criteria are necessary. The Rosemont classification, more restrictive, aims to standardize the criteria and assigns different values to different features, but requires further validation. EUS-fine needle aspiration (EUS-FNA) is less advisable for diagnosis of diffuse CP due to its potential side effects. Elastography and contrast-enhanced EUS are orientation in differentiating a focal pancreatic mass in a parenchyma with features of CP, but they cannot replace EUS-FNA. The usefulness of EUS-guided celiac block for painful CP is still being debated with regard to the best technique and the indications. EUS-guided drainage of pseudocysts is preferred in non-bulging pseudocysts or in the presence of portal hypertension. EUS-guided drainage of the main pancreatic duct should be reserved for cases in which endoscopic retrograde cholangiopancreatography has failed owing to difficult cannulation of the papilla or difficult endotherapy. It should be performed only by highly skilled endoscopists, due to the high rate of complications.


[Prevention and treatment of somatic complications arising from the use of antipsychotics].
Antipsychotics are effective drugs that are prescribed frequently for a large group of patients. However, they also have many side-effects which can lead ultimately to serious somatic complications. These complications fall into various categories: metabolic, cardiovascular, neurobiological, haematological, gastro-intestinal and urogenital. To make an inventory of the side-effects and advise on ways of monitoring and preventing them. method The multidisciplinary working group on somatic complications arising from the use of antipsychotics (Werkgroep Somatische Complicaties) has collected literature on the subject and has discussed it at a number of consensus meetings. results The most frequent somatic complications are described on the basis of specific risk profiles and advice is given on how to identify these complications and on how to treat them when necessary. It is essential to monitor, systematically and regularly, somatic complications arising from the use of antipsychotics; furthermore, polypharmacy should be avoided. The person ultimately responsible for this is the doctor who has prescribed the antipsychotics. In addition, it is important to draw patients' attention to the general rules for a healthy lifestyle: no smoking, a balanced diet and adequate exercise. It is very important that somatic complications should be monitored carefully and accurately. So far, the Netherlands has no official guidelines on ways to identify and treat somatic complications.


Transcriptome in Combination Proteome Unveils the Phenylpropane Pathway Involved in Garlic (Allium sativum) Greening.
Garlic (Allium sativum) is an important vegetable crop that is widely used in cooking and medicine. The greening phenomenon of garlic severely decreases the quality of garlic and hinders garlic processing. To study the mechanism of garlic greening, comprehensive full-length transcript sets were constructed. We detected the differences in greening between Pizhou (PZ) garlic and Laiwu (LW) garlic that were both stored at -2.5°C and protected from light at the same time. The results showed that 60,087 unigenes were respectively annotated to the NR, KEGG, GO, Pfam, eggNOG and Swiss Prot databases, and a total of 30,082 unigenes were annotated. The analysis of differential genes and differential proteins showed that PZ garlic and LW garlic had 923 differentially expressed genes (DEGs), of which 529 genes were up regulated and 394 genes were downregulated. Through KEGG and GO enrichment analysis, it was found that the most significant way of enriching DEGs was the phenylpropane metabolic pathway. Proteomics analysis found that there were 188 differentially expressed proteins (DAPs), 162 up-regulated proteins, and 26 down-regulated proteins between PZ garlic and LW garlic. The content of 10 proteins related to phenylpropanoid biosynthesis in PZ garlic was significantly higher than that of LW garlic. This study explored the mechanisms of garlic greening at a molecular level and further discovered that the formation of garlic green pigment was affected significantly by the phenylpropanoid metabolic pathway. This work provided a theoretical basis for the maintenance of garlic quality during garlic processing and the future development of the garlic processing industries.


Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC peripheral cytomegalovirus retinitis trial. A randomized, controlled trial. Studies of Ocular complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group.
Cytomegalovirus (CMV) retinitis is a common infection and a major cause of visual loss in patients with the acquired immunodeficiency syndrome (AIDS). To evaluate intravenous cidofovir as a treatment for CMV retinitis. Two-stage, multicenter, phase II/III, randomized, controlled clinical trial. Ophthalmology and AIDS services at tertiary care medical centers. 64 patients with AIDS and previously untreated, small, peripheral CMV retinitis lesions (that is, patients at low risk for loss of visual acuity). Patients were randomly assigned to one of three groups: the deferral group, in which treatment was deferred until retinitis progressed; the low-dose cidofovir group, which received cidofovir, 5 mg/kg of body weight once weekly for 2 weeks, then maintenance therapy with cidofovir, 3 mg/kg once every 2 weeks; or the high-dose cidofovir group, which received cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5 mg/kg once every 2 weeks. To minimize nephrotoxicity, cidofovir was administered with hydration and probenecid. Progression of retinitis, evaluated in a masked manner by a fundus photograph reading center; the amount of retinal area involved by CMV; the loss of visual acuity; and morbidity. Median time to progression was 64 days in the low-dose cidofovir group and 21 days in the deferral group (P = 0.052, log-rank test). The median time to progression was not reached in the high-dose cidofovir group but was 20 days in the deferral group (P = 0.009, log-rank test). Analysis of the rates of increase in the retinal area affected by CMV confirmed the data on time to progression. The three groups had similar rates of visual loss. Proteinuria of 2+ or more occurred at rates of 2.6 per person-year in the deferral group, 2.8 per person-year in the low-dose cidofovir group (P > 0.02), and 6.8 per person-year in the high-dose cidofovir group (P = 0.135). No patient developed 4+ proteinuria, but two cidofovir recipients developed persistent elevations of serum creatinine levels at more than 177 mumol/L (2.0 mg/dL). Reactions to probenecid occurred at a rate of 0.70 per person-year. Intravenous cidofovir, high- or low-dose, effectively slowed the progression of CMV retinitis. Concomitant probenecid and hydration therapy, intermittent dosing, and monitoring for proteinuria seemed to minimize but not eliminate the risk for nephrotoxicity.


[Peutz-Jeghers syndrome. Report of a case].
The author describes a case of Peutz-Jeghers' Syndrome, an affection determined by a dominant autosomic gene and which is characterized by pigmentation of the skin and mucosas associated with gastrointestinal polyposis; further it is to be reminded that in distinct pathologies it is also possible to observe the presence of skin lesions and the imperilment of internal organs.